Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

Abstract

Aim of the study Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC. Material and methods A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes. Results A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis. Conclusions Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

“…On the other hand, non-alcoholic steatohepatitis (NASH) related HCC has been shown to accumulate exhausted CD8 + PD1 + T cells in the TME, and in preclinical models, anti-PD-1 therapy instead of tumor regression led to tumor progression in terms of size as well number of nodules[ 50 ]. Another systematic review[ 51 ] showed the non-inferiority of LEN to Atez/Bev in achieving an objective response rate (ORR) and disease control rate (DCR) in advanced HCC; however, data were insufficient for evaluation of OS.…”